Where investment dollars are headed
As you might imagine, self-cancer diagnosis are often frowned upon by physicians, but there are few cancers where self-awareness is more paramount to early detection than skin cancer. Therefore, the majority of research and development dollars isn’t being spent on early detection. Instead, biopharmaceutical companies have focused their efforts on bettering and extending the quality of life for patients with advanced melanoma.
Zelboraf: Don’t be shocked, but once again Roche Holding Ltd. (OTCBB:RHHBY) has a go-to drug in a commonly diagnosed cancer. Zelboraf is a twice-daily oral medication approved by the FDA in August 2011 to treat metastatic melanoma. Specifically, Zelboraf targets a mutation known as BRAF-V600E, which it can detect through a test it provided by LabCorp. In a head-to-head trial with Dacarbazine (discussed below), Zelboraf delivered progression-free survival of 5.3 months and a median overall survival of 16 months. For Dacarbazine, its PFS was merely 1.6 months and median overall survival was 7.9 months. The biggest adverse side effect of Zelboraf was the development of non-melanoma skin cancers in 24% of clinical patients; however, non-melanoma cancers are considerably easier to treat.
Yervoy: Yervoy is an intravenous immunotherapy developed by Bristol Myers Squibb Co. (NYSE:BMY) that was approved in March 2011 for unresectable or metastatic melanoma. I know what you’re thinking, “Why not take oral Zelboraf, because who wants an IV?” However, a full regimen of Yervoy would only be four infusions, each given three weeks apart from the last. In trials when compared against a tumor vaccine, median overall survival for Yervoy was 10 months compared to just six months for the tumor vaccine alone. Overall response rates were clearly in Yervoy’s favor as well, with 5.7% of patients in the Yervoy plus vaccine arm responding compared to just 1.5% for the vaccine control arm. Adverse events were also considerably less severe with immunological side effects knocking just 10% of patients out of trials. The downside, of course, is Yervoy’s outrageous $120,000 price, which can create patient, insurance, and physician reimbursement concerns.
Dacarbazine (DTIC-Dome): Dacarbazine, known as DTIC-Dome, was originally developed by Bayer in the mid-1970s and is an intravenously administered chemotherapy agent. As you might imagine, its patents have long since expired and generic competition comes from numerous other producers, although Bayer still produces DTIC-Dome. The drug works in the liver and acts by altering the DNA of cancer cells to slow their growth. Fortunately, advancements in medication since DTIC-Dome have been impressive because the response rate for the drug is relatively low, and the side effects, including liver complications, can be fairly serious.
Proleukin: Like Dacarbazine above, you won’t see Proleukin used as often anymore, but it’s still a therapy worth mentioning. Developed originally by Chiron, which was purchased by Novartis AG (ADR) (NYSE:NVS) in 2005, Proleukin is an intravenous agent administered three times daily for a total of five days. Depending on how well the patient responds, the dosing can be repeated after nine days. It was originally approved in January 1998 after a complete or partial response was noted in 16% of clinical patients. In 2010, Novartis sold its U.S. rights to Proleukin to Prometheus Laboratories.
As is the case with all the previous commonly diagnosed cancers that have preceded melanoma, there have been quite a few cases of failure. Synta Pharmaceuticals Corp. (NASDAQ:SNTA) lost 79% of its share value in a single day after halting a metastatic melanoma trial in 2009 for experimental drug Elesclomol. In trials, more patients died taking Elesclomol than in the paclitaxel control arm, thus prompting the company to halt development of the drug. Even Pfizer Inc.‘s Tremelimumab has felt the pangs of rejection — twice! After dropping development of the drug in 2008 following its failure to show a statistical advantage over the placebo, Pfizer revived the program only to see similar non-statistically significant results as a first-line metastatic melanoma treatment in January of this year.
What’s coming down the pipeline
Now that we have a better idea of what types of treatments are available for those with metastatic melanoma, let’s have a look at some of the revolutionary therapies that are coming down the pipeline.
Talimogene laherparepvec: Aside from having a name that sounds like it was made up by a Klingon, this experimental drug is injected directly into the lesion tissue and then replicates until the cell membranes of cancer cells rupture in a process known as cell lysis. Upon cell death, GM-CSF is released, which is a white-blood cell growth factor that activates the body’s own immune system to attack cancer cells. Owned by Amgen, Inc. (NASDAQ:AMGN) through the purchase of BioVax, Talimogene laherparepvec delivered a durable response rate of at least six months in 16% of patients in late-stage trials compared to just 2% for the control arm. Although median overall survival rates have yet to be determined — the initial results of this trial were released by Amgen, Inc. (NASDAQ:AMGN) just two weeks ago – it appears that median survival would be expected to improve for the Talimogene laherparepvec arm.
Dabrafenib and Trametinib: The combination of Dabrafenib — a BRAF inhibitor similar to Zelboraf — and Trametinib — an MEK 1/2 inhibitor — recently delivered favorable results in a mid-stage study undertaken by GlaxoSmithKline plc (ADR) (NYSE:GSK). BRAF mutations occur in about half of all metastatic melanoma cases, so this combo will target a good chunk of the advanced melanoma population, but patients often develop resistances to Dabrafenib after just five to seven months. The addition of Trametinib acts to extend the duration of response by blocking the MEK protein, which attacks BRAF and could help to reduce the adverse side effects often seen in BRAF-inhibitors, like non-melanoma cancer development. In trials, progression-free survival jumped to 9.4 months for the combo arm versus just 5.8 months for Dabrafenib alone. Even more impressively, at 12 months, 41% of patients in the combo trial had not seen any disease progression compared to only 9% in the Dabrafenib-only control arm.
Your best investment
Death risk associated with many skin cancers aren’t very high, but the research and development dollars being poured into improving the quality of life with regard to melanoma therapies certainly isn’t chump change.
If you’re willing to roll the dice a bit, I’m very intrigued by the combination treatment in mid-stage development by GlaxoSmithKline plc (ADR) (NYSE:GSK). We’ve seen plenty of therapies fail in late-stage treatments, so don’t count your chickens before they’re hatched, but Glaxo appears to have discovered a novel way to counter a patients’ BRAF resistance while also potentially reducing many of the serious side effects associated with BRAF-inhibiting drugs.
As much as it pains me to say this, because I feel CEO Lamberto Andreotti has done a miserable job leading his company, Bristol Myers Squibb Co. (NYSE:BMY) looks like the safest investment in treating melanoma. Yervoy has the advantage of being a first-line treatment which gives Bristol Myers Squibb Co. (NYSE:BMY) the opportunity to market to a much broader audience than many metastatic melanoma drugs. That, coupled with its $120,000 price tag and the potential for additional indications, makes it the most promising long-term melanoma treatment.
Stay tuned next week when we tackle the current and upcoming therapies for the treatment of bladder cancer in this Tackling Cancer series.
The article Tackling Cancer: Melanoma’s Biggest Current & Upcoming Players originally appeared on Fool.com.
Fool contributor Sean Williams has no material interest in any companies mentioned in this article. You can follow him on CAPS under the screen name TMFUltraLong, track every pick he makes under the screen name TrackUltraLong, and check him out on Twitter, where he goes by the handle @TMFUltraLong.The Motley Fool recommends Laboratory of America.
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